摘要Background Recent studies have shown that sodium-glucose cotransporters-2(SGLT2)inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction(HFpEF)patients,but the exact mechanism is un-known.Ferritinophagy is a special form of selective autophagy that participates in ferroptosis.In this study,we aimed to invest-igate whether ferritinophagy was activated during the occurrence of HFpEF,and whether canagliflozin(CANA)could inhibite ferritinophagy.Methods We reared Dahl salt-sensitive(DSS)rats on a high-salt diet to construct a hypertensive HFpEF model,and simultan-eously administered CANA intervention.Then we detected indicators related to ferritinophagy.Results The expression of nuclear receptor coactivator 4(NCOA4),as well as microtubule-associated proteins light chain 3(LC3),Bcl-2 interacting protein 1(Beclin-1)and p62,were upregulated in HFpEF rats,accompanied by the downregulation of fer-ritin heavy chain 1(FTH1),upregulation of mitochondrial iron transporter sideroflexin1(SFXN1)and increased reactive oxygen species(ROS)production.Above changes were diminished by CANA.CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA,leading to HFpEF benefits.The inhibi-tion of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF,and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.